Internal Fat's Role In Type 2 Diabetes Probed

A new study - made possible by the seamless collaboration of no less than nine distinct operating units - will test how patients' insulin sensitivity is affected by removal of the omentum, a blanket of internal abdominal fat that rests on top of the intestines and is attached to both the stomach and the small bowel.

The study, led by Naji Abumrad, M.D., professor and chair of General Surgery, will combine the removal of the omentum with gastric bypass surgery.

The investigation is a novel approach to treating type 2 diabetes, but has its basis in years of obesity and diabetes-related research, Abumrad said.

“The world community has spent a tremendous amount of time looking at the relationship of weight and type 2 diabetes. It's known that the higher the weight, the higher the chance of developing type 2 diabetes,” Abumrad said. “We have also shown the reversal of this through gastric bypass surgery. We know that this surgery leads to significant weight loss and a significant resolution of diabetes. We wanted to know how the reversal occurred - what were the predictive variables that led to resolution of diabetes.”

With Alfonso Torquati, M.D., assistant professor of Surgery, Abumrad learned that the only weight-loss variable of sufficient determining power in the reduction of type 2 diabetes is waist circumference.

“The larger the waist circumference, the higher the incidence of type 2 diabetes,” Abumrad said. “So we started asking - what is it about waist circumference that is so predictive?”

The answer could be the internal or visceral fat padding the waistline. Studies have shown that removing large amounts of abdominal fat on the periphery through liposuction does not affect insulin sensitivity. Therefore, Abumrad said, they are looking at the fat inside the belly, most of which is located in the omentum.

“We decided to take the concept to the lab first,” he said. In animal studies, they tested insulin sensitivity and how the liver and muscle metabolize sugar both before and after removing the visceral fat. They found after removing the omentum, the liver cuts down production of sugar by nearly 40 percent.

“The effect of the omentum on the liver is quite powerful,” Abumrad said. “This is as effective in shutting down the liver production of insulin as many of the drugs being used to treat type 2 diabetes. We also observed one additional surprising finding: Removing the omentum also increased the consumption of sugar by the peripheral tissues, primarily skeletal muscle.”

The team will test omentum removal in morbidly obese adults. Participants will be randomized to either a Roux-en-Y gastric bypass surgery with omentum removal or a Roux-en-Y gastric bypass surgery alone. The researchers will compare the participants' insulin sensitivity before and after the surgery, as well as comparing the participants to one another to understand what variables might affect the speed of response to the surgery and to a reversal in type 2 diabetes.

The collaboration of a large team of VUMC physicians and researchers will expand the focus of the investigation to include metabolic implications, genetic aspects of obesity and diabetes such as racial differences, pharmacological concerns including chronic inflammation, and cardiovascular elements.

“We have put an incredible team together - something I could only do at Vanderbilt and nowhere else,” Abumrad said. Collaborators include members of the Department of General Surgery, the Center for Human Nutrition, the Dayani Center, the Division of Diabetes, the Department of Medicine, the Center for Nutrition Research Unit, the Division of Genetic Medicine, the Division of Clinical Pharmacology, as well as the Division of Cardiovascular Medicine.

Currently, there are no known risks to removing the omentum. It is commonly removed during surgery for ovarian cancer, but has never before been removed solely for the purpose of treating type 2 diabetes.

The five-year study is funded by a grant from the National Institutes of Health and will include 120-160 patients. Half of the participants will have their omentum removed along with gastric bypass surgery, half will not. In an effort to compare racial differences in type 2 diabetes, the study is seeking an equal number of African-American participants and Caucasian participants.